Modeling temporal behavior of postnatal cat retinal ganglion cells

During development, mammalian retinal ganglion cells (RGCs) go through mark ed ontogenetic changes with respect to their excitable membrane properties. Voltage-clamp studies conducted in our laboratory have shown that the ampl itude, voltage-dependence and kinetics of activation and inactivation (wher e present) of Na+, K+ and Ca2+ conductances all exhibit developmental chang es during a time when the firing patterns of mammalian ganglion cells shift from being transient to being predominantly sustained in nature. In order to better understand the contribution of each conductance to the generation of spikes and spiking patterns, we have developed a model based on our exp erimental data. For simplicity, we have initially used experimental data ob tained from postnatal ganglion cells. At this age the ontogenetic changes o bserved in the characteristics of the various ionic currents are complete. Utilizing the methods adopted by Hodgkin and Huxley for the giant squid axo n, we have determined rate equations for the activation and inactivation pr operties of the I-A, I-Kdr, I-Na, I-CaL, I-CaN, and I-leak currents in post natal cat RGCs. Combining these with a simplified model of the calcium-acti vated potassium current (I-KCa), we have solved and analysed the resulting differential equations. While spikes and spiking patterns resembling experi mental data could be obtained from a model in which [Ca-i(2+)] was averaged across the whole cell, more accurate simulations were obtained when the di ffusion of intracellular Ca2+ was modeled spatially. The resulting spatial calcium gradients were more effective in gating I-KCa, and our simulations more accurately matched the recorded amplitude and shape of individual spik es as well as the frequency of maintained discharges observed in mammalian postnatal RGCs. (C) 2001 Academic Press.